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One-Year Brain Structural Changes Are Associated with Postoperative Delirium and Delayed Resolution of Interleukin-6

Lv, J.; Taylor, J.; Curtis, S.; Kramer, K.; Kunkel, D.; Thakur, S.; Nair, V.; Banks, M. I.; Pearce, R. A.; Prabhakaran, V.; Lennertz, R.; Sanders, R. D.

2026-05-08 neurology
10.64898/2026.05.03.26352074 medRxiv
Show abstract

BackgroundPostoperative delirium is a common complication in older adults and is associated with neuroinflammation and cognitive decline. Previous studies have shown that the number of surgical procedures is associated with hippocampal volume loss in older adults in a large-scale UK Biobank study. However, it remains unclear whether hippocampal volume loss within one year after surgery is associated with postoperative delirium. MethodsLongitudinal structural MRI data and blood biomarkers were collected before surgery and one year postoperatively from 62 participants (>65 years, 27 females) undergoing major non-intracranial surgery. Hippocampal and other subcortical volumes were quantified using FreeSurfer. Cortical thickness was measured for cortical regions defined by the Desikan-Killiany (DK) atlas. One-year structural changes were examined in relation to peak Delirium Rating Scale (DRS) scores and one-year changes in plasma interleukin (IL)-6 levels. ResultsOne-year volume loss in the right hippocampus was significantly correlated with postoperative peak DRS scores and the one-year change in IL-6. Additional gray matter reductions were observed in the right putamen and the right superior parietal cortex. Right putamen volume loss was also associated with the one-year change in IL-6, while cortical thinning in the right superior parietal cortex was associated with peak DRS scores. ConclusionsPostoperative delirium is associated with longitudinal gray matter loss following surgery. Delayed resolution of inflammation may also contribute to postoperative brain structural changes. Clinical trial registrationNCT01980511 and NCT03124303.

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